The experiments in this proposal address two basic problems in neurobiology: at what stage of a neuron's development does its fate become restricted to a specific cell type and what factors regulate neuron number in the CNS. To answer these questions, I propose to analyze events during the earliest stages of nervious system formation. Many experiments have shown, in lower vertebrates, that the regional information in transplantable pieces of neural plate is intrinsic to the piece itself. While this stage of mammalian development is inaccesible to direct experimental manipulations, data recently assembled in my lab raise the issue of whether in addition to this regional specificity, the fates of the early neuroblasts may have become quite specific. Our counts of Purkinje cells in lurcher chimeric mice suggest that there are only 8 prognetior cells that undergo the spatial/genetic restrictions which specify that only the descendents of these cells shal produce Purkinje cells. I calculate the restricion must occur around the neural plat/neural fold stage of development. To pursue these observations I will look for evidence that cell types known to be developmentally related to Purkinje cells (such as Golgi cells and deep nuclear neurons) share a common or disparate cell lineage. Further, I will search for conditions which alter the number of Purkinje cells progenitors. Inbred strains of mice which differ in their adult number of Purkinje cells will be sought. Chimeras of these strains will reveal whether the difference is due to different numbers of progenitors or to other factors. These studies of early restriction of cell fates and process involved in determination of cell number in the CNS are rarely approached in a mammal. The use of the mouse as a model furthers my belief that the findings will bear directly on human development and developmental disorders. Finally, as an end in itself and as an adjunct to the other studies of this project, a new and more accurate method of cell counting will be developed.